The proposed research is to study biochemical processes in the initiation and control of erythropoiesis at the cellular level. The approach is directed at characterizing the mechanism of erythropoietin- stimulated delta-aminolevulinic acid synthetase and the role of cyclic AMP in red cell production. Erythropoietin and cyclic AMP effects will be analyzed in marrow cultures as well as in vivo with kinetic experiments of enzyme induction at various stages of erythropoietic cell development. The effect of erythropoietin on cyclic AMP production will be explored. The influence of other physiological regulating factors of hemopoiesis (e.g., inhibitors, natural steroids) will be examined in these systems. Selected methods in this approach will be applied in the study of animal models of anemia. A search for biosynthetic defects during the events of red cell production and in the regulation of hemopoiesis will be undertaken in refractory and hypoplastic anemias. Activities of enzymes of heme biosynthesis and their in vitro response to physiological stimulants (e.g., erythropoietin, cyclic AMP), and possible abnormal plasmatic factors will be correlated with in vivo levels of erythropoietin activity.